Portal Hypertension In Dogs Research Articles

Plasma renin activity and aldosterone concentration in dogs with acquired portosystemic collaterals

BackgroundThe renin‐angiotensin‐aldosterone system (RAAS) is activated in humans with portal hypertension (PH) associated with liver disease. However, involvement of RAAS in dogs with intrahepatic PH is not clear.ObjectiveTo measure plasma renin activity (PRA) and plasma aldosterone concentration (PAC) in dogs with PH (chronic hepatitis [CH] and primary hypoplasia of the portal vein [PHPV]), dogs with extrahepatic congenital portosystemic shunt (EH‐CPSS), and healthy dogs and to determine whether the RAAS is activated in dogs with PH.AnimalsTwenty‐seven dogs with acquired portosystemic collaterals (APSCs; 15 dogs with CH, 12 dogs with PHPV), 9 dogs with EH‐CPSS, and 10 healthy dogs.MethodsRetrospective study. Plasma renin activity and PAC were measured by radioimmunoassay.ResultsPlasma renin activity was significantly higher in the CH group (median, 4.4 ng/mL/h) than in the EH‐CPSS (median, 1.0 ng/mL/h; P < .01) and the healthy (median, 1.1 ng/mL/h; P < .01) groups. No significant differences were found between the PHPV group (median, 2.2 ng/mL/h) and other groups. Plasma aldosterone concentration was significantly higher in the CH (median, 111.0 pg/mL) and PHPV (median, 89.5 pg/mL) groups than in the EH‐CPSS (median, 1.0 pg/mL; P < .001, P < .01, respectively) and healthy (median, 14.5 pg/mL; P < .001, P < .05, respectively) groups.Conclusions and Clinical ImportanceActivation of the RAAS contributes to the pathophysiology of intrahepatic PH in dogs, suggesting that spironolactone may not only be effective for the treatment of ascites but also for the suppression of intrahepatic PH.

Assessment of contrast-enhanced ultrasonography of the hepatic vein for detection of hemodynamic changes associated with experimentally induced portal hypertension in dogs.

OBJECTIVE To assess the use of contrast-enhanced ultrasonography (CEUS) of the hepatic vein for the detection of hemodynamic changes associated with experimentally induced portal hypertension in dogs. ANIMALS 6 healthy Beagles. PROCEDURES A prospective study was conducted. A catheter was surgically placed in the portal vein of each dog. Hypertension was induced by intraportal injection of microspheres (10 to 15 mg/kg) at 5-day intervals via the catheter. Microsphere injections were continued until multiple acquired portosystemic shunts were created. Portal vein pressure (PVP) was measured through the catheter. Contrast-enhanced ultrasonography was performed before and after establishment of hypertension. Time-intensity curves were generated from the region of interest in the hepatic vein. Perfusion variables measured for statistical analysis were hepatic vein arrival time, time to peak, time to peak phase (TTPP), and washout ratio. The correlation between CEUS variables and PVP was assessed by use of simple regression analysis. RESULTS Time to peak and TTPP were significantly less after induction of portal hypertension. Simple regression analysis revealed a significant negative correlation between TTPP and PVP. CONCLUSIONS AND CLINICAL RELEVANCE CEUS was useful for detecting hemodynamic changes associated with experimentally induced portal hypertension in dogs, which was characterized by a rapid increase in the intensity of the hepatic vein. Furthermore, TTPP, a time-dependent variable, provided useful complementary information for predicting portal hypertension. IMPACT FOR HUMAN MEDICINE Because the method described here induced presinusoidal portal hypertension, these results can be applied to idiopathic portal hypertension in humans.

Three Minimally Invasive Methods of Measuring of Portal Vein Pressure in Healthy Dogs

We compared wedged hepatic venous pressure (WHVP), splenic pulp pressure (SPP) and trans-splenic portal vein pressure (TSPVP) in healthy dogs. We found that portal blood pressure could be measured in dogs using any of these techniques. The WHVP, SPP and TSPVP were 7.8 ± 1.0, 6.2 ± 0.8 and 6.8 ± 1.2 mmHg, respectively. Measuring SPP using ultrasound is most simple and minimally invasive, and it might be useful for evaluating portal hypertension in dogs with liver diseases.

A canine portal hypertension model induced by intra‐portal administration of Sephadex microsphere

Big animal models of portal hypertension are important for the research into this disease. The aim of this study was to establish a canine portal hypertension model by intra-portal administration of microspheres. Sixteen mongrel dogs were assigned to control group and experimental group randomly. The catheterization of portal vein was performed by laparotomy and the outer end of the catheter was fixed subcutaneously in the abdominal wall. The dogs of the experimental group were given intra-portal injections of microspheres at a five-day interval, six times in total. Portal hemodynamics, blood cell counting, liver and renal function test, portography, gastroscopy, liver, spleen and lung histological examination were taken to evaluate the model. 1, 2, 3 and 4 months after initial injection of microspheres, portal venous pressure rose from baseline 8.7 +/- 0.7 mmHg to 24.3 +/- 1.6, 20.6 +/- 2.1, 19.0 +/- 1.8 and 17.7 +/- 2.0 mmHg, respectively (P < 0.01). The diameter of portal vein increased from 7.6 +/- 0.3 to 8.6 +/- 0.3 mm, calculated portal resistance increased from 0.46 +/- 0.06 to 1.06 +/- 0.20 (mmHg/mL/min/kg body weight); velocity of portal blood flow decreased from 35.1 +/- 1.7 to 26.1 +/- 2.4 cm/s (P < 0.01, respectively). The animals of experimental group developed marked splenomegaly and profuse portosystemic collateral circulations with normal liver and renal function. Repeated intra-portal administration of microspheres can induce stable and reproducible chronic portal hypertension in dogs with normal liver and renal functions. This model can meet multiple demands of both basic and clinical research of portal hypertension.

Ascites due to pre‐sinusoidal portal hypertension in dogs: a retrospective analysis of 17 cases

Accumulation of a pure transudate abdominal effusion in the absence of significant hypoalbuminaemia is uncommon in dogs and is due to pre-sinusoidal portal hypertension. Reported causes of pre-sinusoidal portal hypertension vary, but suggest a reasonable prognosis. A retrospective analysis of 17 dogs that presented to our institution with ascites due to pre-sinusoidal portal hypertension identified idiopathic hepatic fibrosis or canine chronic hepatitis as the underlying cause in the majority of cases. Twelve (70.5%) dogs were 4 years of age or younger at time of presentation. Total serum protein was higher in dogs with chronic hepatitis than it was in dogs without inflammatory disease. The prognosis was generally poor and no histological, imaging or biochemical parameters were useful as prognostic indicators. Dogs died or were euthanased due to severe clinical signs associated with the portal hypertension and/or perceived poor prognosis.

The role of spleno-pulmonary parenchymatous anastomosis in the reduction of portal hypertension in dogs.

The role of spleno-pulmonary parenchymatous anastomosis in the reduction of portal hypertension in dogs.

Serum‐Effusion Albumin Gradient in Dogs with Transudative Abdominal Effusion

A prospective clinical study in dogs with transudative abdominal effusions examined the clinical usefulness of the serum albumin‐effusion albumin (SA‐EA) gradient. In humans, the SA‐EA gradient facilitates classification of abdominal effusion, with a gradient ≥1.1 indicating the presence of portal hypertension. Gradient values proved useful for predicting therapeutic response to sodium restriction and diuresis in humans. Of 49 dogs evaluated, 25 had hepatobiliary disease (group 1) and 24 had other nonhepatobiliary conditions (group 2). Portal hypertension was clinically suspected in 24 of 25 dogs in group 1 and in 15 of 24 dogs in group 2. A broad range of SA‐EA gradients was found. A gradient ≥1.1 was found in 22 of 25 (88.0%) dogs with liver disease and in 14 of 24 (58.3%) dogs with other disorders. The median SA‐EA gradient was higher in group 1 than in group 2, with values of 1.4 (range, 0.7–3.1) and 1.1 (range, 0.3–2.6), respectively (P &lt; .04). Considerable overlapping of SA‐EA gradients occurred between groups and among dogs with diverse conditions such that gradient values could not distinguish dogs with hepatobiliary disease from dogs with other conditions. The overall diagnostic accuracy of the SA‐EA gradient in predicting portal hypertension in dogs with and without hepatobiliary disease (69.4%) exceeded that of hypoalbuminemia (57.1%). These findings suggest that portal hypertension is a predominant force in formation of transudative abdominal effusion in dogs with hepatobiliary disease and in dogs with other disorders. Whether the SA‐EA gradient can be used to guide therapeutic mobilization of effusion in dogs remains to be proved.

Serum-effusion albumin gradient in dogs with transudative abdominal effusion.

A prospective clinical study in dogs with transudative abdominal effusions examined the clinical usefulness of the serum albumin-effusion albumin (SA-EA) gradient. In humans, the SA-EA gradient facilitates classification of abdominal effusion, with a gradient > or = 1.1 indicating the presence of portal hypertension. Gradient values proved useful for predicting therapeutic response to sodium restriction and diuresis in humans. Of 49 dogs evaluated, 25 had hepatobiliary disease (group 1) and 24 had other nonhepatobiliary conditions (group 2). Portal hypertension was clinically suspected in 24 of 25 dogs in group 1 and in 15 of 24 dogs in group 2. A broad range of SA-EA gradients was found. A gradient > or = 1.1 was found in 22 of 25 (88.0%) dogs with liver disease and in 14 of 24 (58.3%) dogs with other disorders. The median SA-EA gradient was higher in group 1 than in group 2, with values of 1.4 (range, 0.7-3.1) and 1.1 (range, 0.3-2.6), respectively (P < .04). Considerable overlapping of SA-EA gradients occurred between groups and among dogs with diverse conditions such that gradient values could not distinguish dogs with hepatobiliary disease from dogs with other conditions. The overall diagnostic accuracy of the SA-EA gradient in predicting portal hypertension in dogs with and without hepatobiliary disease (69.4%) exceeded that of hypoalbuminemia (57.1%). These findings suggest that portal hypertension is a predominant force in formation of transudative abdominal effusion in dogs with hepatobiliary disease and in dogs with other disorders. Whether the SA-EA gradient can be used to guide therapeutic mobilization of effusion in dogs remains to be proved.

Depressor response during experimental portal hypertension in dog.

Elevation of splanchnic portal pressure in dogs results in an apparently reflexic response manifest as an active reduction in mean arterial pressure (AP). The results from 14 dogs separated into a tachycardic (TACH) heart rate (HR) response (P less than 0.005, n = 6) group and a bradycardic (BRAD) HR response (P less than 0.005, n = 8) group. Both groups showed similar reductions in AP and cardiac output (CO); however, stroke volume (SV) was reduced to a greater extent (P less than 0.029) in the TACH group. Atropine eliminated or reversed the bradycardia in the BRAD group and propranolol blocked the tachycardia in the TACH group. When portal hypertension was repeated in the BRAD group after atropine, similar reductions (P less than 0.01) were observed in AP, SV, and CO but total peripheral resistance (TPR) no longer increased. Reductions in SV or CO due to reduced venous return only partially explain the AP changes. These data suggest the reflex activation of several mechanisms that contribute to rather than completely oppose the reduction in AP anticipated with a reduction in venous return. They include an atropine-sensitive negative chronotropic effect and a negative inotropic effect as well as adjustments in TPR. We thus propose a reflex mechanism that is activated by increased splanchnic pressure and contributes to an active lowering of mean arterial pressure.

Experimental production of portal hypertension in dogs by a whole liver compression.

In spite of many attempts to produce an experimental model for studying the pathogenesis and the pathophysiology of portal hypertension and esophageal varices, satisfactory results have not been reported. Since most attempts involved multiple operations or complicated surgical maneuvers to achieve portal hypertension, experimental animals could not survive easily. This new procedure requires only a simple operation, so experimental animal survival is high. The portal venous pressure can be raised immediately by increasing intrahepatic vascular resistance. This is done by wrapping and compressing the whole liver with polypropylene mesh, which also prevents the development of hepatopetal collaterals. The experimental production of portal hypertension in fifteen dogs resulted in only one death. The remaining fourteen dogs were in good condition for nine weeks after the operation and were maintaining elevated ranges of portal pressure with an average of 326 mmH2O. Varying degrees of esophageal venous dilatation were evident. Based on the results, this newly developed method seems to be useful for studying the pathophysiology of the portal hypertension and esophageal varices.

Nonthrombogenic extracorporeal portosystemic shunt.

In spite of ideal present day management, 25% of patients who bleed from esophageal varices continue to succumb to hemorrhage. Those who fail to respond to conservative measures require surgical intervention. Major surgery on a patient already taxed by exsanguinating hemorrhage and hepatic decompensation is accompanied by a high mortality. White et al,1Piccone and LeVeen,2and Christopherson et al3have recently described the use of an umbilical systemic vein shunt with low operative mortality to control bleeding from esophageal varices. Their reports indicate that flows obtained under existing portosystemic pressure differentials were sufficient to abate exsanguination. Gott et al4have described a non thrombogenic coating technique for surfaces using graphite, heparin sodium, and benzalkonium chloride. Zarins et al5have recently reported their results with splenofemoral or external jugular shunts to relieve portal hypertension in dogs utilizing the Gott graphite-benzalkonium-heparin coating. We6have developed

Attempts at the experimental production of portal hypertension.

VON ECK1first produced a portacaval fistula in dogs in 1877, and he performed eight such operations. In this operation the portal vein was ligated between the anastomosis and the liver. Other reports since this time by Pavlov,2Freeman3and others have indicated that a fistula produced in this manner will remain patent. In our hands the production of such a fistula in the dog without portal obstruction results in closure of the fistula in approximately one third of the cases in three to six weeks. It seemed important to produce chronic portal hypertension in dogs to determine whether a similar frequency of closure occurred in the portacaval fistulas before applying the procedure to human beings. Chronic portal hypertension has been produced by Kershner, Hooton and Shearer4in the dog by partial obstruction of the inferior vena cava. This procedure was not applicable in our experiments,